Unique human immune signature of Ebola virus disease in Guinea

Paula Ruibal; Lisa Oestereich; Anja Lüdtke; Beate Becker-Ziaja; David Wozniak; Romy Kerber; Misa Korva; Mar Cabeza-Cabrerizo; Joseph Bore; Fara Raymond Koundouno; Sophie Duraffour; Romy Weller; Anja Thorenz; Eleonora Cimini; Domenico Viola; Chiara Agrati; Johanna Reptis; Babak Afrough; Lauren Cowley; Didier Ngabo; Julia Hinzmann; Marc Mertens; Ines Vitoriano; Christopher Logue; Jan Peter Boettcher; Elisa Pallasch; Andreas Sachse; Amadou Bah; Katja Nitzsche; Eeva Kuisma; Janine Michel; Tobias Holm; Elsa-Gayle Zekeng; Isabel García-Dorival; Roman Wölfel; Kilian Stoecker; Erna Fleischmann; Thomas Strecker; Antonino Di Caro; Tatjana Avšič-Županc; Andreas Kurth; Silvia Meschi; Stephane Mély; Edmund Newman; Anne Bocquin; Zoltan Kis; Anne Kelterbaum; Peter Molkenthin; Fabrizio Carletti; Jasmine Portmann; Svenja Wolff; Concetta Castilletti; Gordian Schudt; Alexandra Fizet; Lisa Ottowell; Eva Herker; Thomas Jacobs; Birte Kretschmer; Ettore Severi; Nobila Ouedraogo; Mar Lago; Anabel Negredo; Leticia Franco; Pedro Anda; Stefan Schmiedel; Benno Kreuels; Dominic Wichmann; Marylyn Addo; Ansgar Lohse; Hilde De Clerck; Carolina Nanclares; Sylvie Jonckheere; Michel Van Herp; Armand Sprecher; Gao Xiaojiang; Mary Carrington; Osvaldo Miranda; Carlos Castro; Martin Gabriel; Patrick Drury; Pierre Formenty; Boubacar Diallo; Lamine Koivogui; N'Faly Magassouba; Miles Carroll; Stephan Günther; Cesar Muñoz-Fontela

doi:10.1038/nature17949

Unique human immune signature of Ebola virus disease in Guinea

Paula Ruibal, Lisa Oestereich, Anja Lüdtke, Beate Becker-Ziaja, David Wozniak, Romy Kerber, Misa Korva, Mar Cabeza-Cabrerizo, Joseph Bore, Fara Raymond Koundouno, Sophie Duraffour, Romy Weller, Anja Thorenz, Eleonora Cimini, Domenico Viola, Chiara Agrati, Johanna Reptis, Babak Afrough, Lauren Cowley, Didier NgaboJulia Hinzmann, Marc Mertens, Ines Vitoriano, Christopher Logue, Jan Peter Boettcher, Elisa Pallasch, Andreas Sachse, Amadou Bah, Katja Nitzsche, Eeva Kuisma, Janine Michel, Tobias Holm, Elsa-Gayle Zekeng, Isabel García-Dorival, Roman Wölfel, Kilian Stoecker, Erna Fleischmann, Thomas Strecker, Antonino Di Caro, Tatjana Avšič-Županc, Andreas Kurth, Silvia Meschi, Stephane Mély, Edmund Newman, Anne Bocquin, Zoltan Kis, Anne Kelterbaum, Peter Molkenthin, Fabrizio Carletti, Jasmine Portmann, Svenja Wolff, Concetta Castilletti, Gordian Schudt, Alexandra Fizet, Lisa Ottowell, Eva Herker, Thomas Jacobs, Birte Kretschmer, Ettore Severi, Nobila Ouedraogo, Mar Lago, Anabel Negredo, Leticia Franco, Pedro Anda, Stefan Schmiedel, Benno Kreuels, Dominic Wichmann, Marylyn Addo, Ansgar Lohse, Hilde De Clerck, Carolina Nanclares, Sylvie Jonckheere, Michel Van Herp, Armand Sprecher, Gao Xiaojiang, Mary Carrington, Osvaldo Miranda, Carlos Castro, Martin Gabriel, Patrick Drury, Pierre Formenty, Boubacar Diallo, Lamine Koivogui, N'Faly Magassouba, Miles Carroll, Stephan Günther, Cesar Muñoz-Fontela

Research output: Contribution to journal › Letter › peer-review

149 Citations (SciVal)

Abstract

Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD1. In particular, very little is known about human immune responses to Ebola virus2,3. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4+ and CD8+ T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.

Original language	English
Pages (from-to)	100-104
Number of pages	5
Journal	Nature
Volume	533
Early online date	4 May 2016
DOIs	https://doi.org/10.1038/nature17949
Publication status	Published - 5 May 2016

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Ruibal, P., Oestereich, L., Lüdtke, A., Becker-Ziaja, B., Wozniak, D., Kerber, R., Korva, M., Cabeza-Cabrerizo, M., Bore, J., Koundouno, F. R., Duraffour, S., Weller, R., Thorenz, A., Cimini, E., Viola, D., Agrati, C., Reptis, J., Afrough, B., Cowley, L., ... Muñoz-Fontela, C. (2016). Unique human immune signature of Ebola virus disease in Guinea. Nature, 533, 100-104. https://doi.org/10.1038/nature17949

Ruibal, P, Oestereich, L, Lüdtke, A, Becker-Ziaja, B, Wozniak, D, Kerber, R, Korva, M, Cabeza-Cabrerizo, M, Bore, J, Koundouno, FR, Duraffour, S, Weller, R, Thorenz, A, Cimini, E, Viola, D, Agrati, C, Reptis, J, Afrough, B, Cowley, L, Ngabo, D, Hinzmann, J, Mertens, M, Vitoriano, I, Logue, C, Boettcher, JP, Pallasch, E, Sachse, A, Bah, A, Nitzsche, K, Kuisma, E, Michel, J, Holm, T, Zekeng, E-G, García-Dorival, I, Wölfel, R, Stoecker, K, Fleischmann, E, Strecker, T, Di Caro, A, Avšič-Županc, T, Kurth, A, Meschi, S, Mély, S, Newman, E, Bocquin, A, Kis, Z, Kelterbaum, A, Molkenthin, P, Carletti, F, Portmann, J, Wolff, S, Castilletti, C, Schudt, G, Fizet, A, Ottowell, L, Herker, E, Jacobs, T, Kretschmer, B, Severi, E, Ouedraogo, N, Lago, M, Negredo, A, Franco, L, Anda, P, Schmiedel, S, Kreuels, B, Wichmann, D, Addo, M, Lohse, A, De Clerck, H, Nanclares, C, Jonckheere, S, Van Herp, M, Sprecher, A, Xiaojiang, G, Carrington, M, Miranda, O, Castro, C, Gabriel, M, Drury, P, Formenty, P, Diallo, B, Koivogui, L, Magassouba, NF, Carroll, M, Günther, S & Muñoz-Fontela, C 2016, 'Unique human immune signature of Ebola virus disease in Guinea', Nature, vol. 533, pp. 100-104. https://doi.org/10.1038/nature17949

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title = "Unique human immune signature of Ebola virus disease in Guinea",

abstract = "Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD1. In particular, very little is known about human immune responses to Ebola virus2,3. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4+ and CD8+ T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.",

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T1 - Unique human immune signature of Ebola virus disease in Guinea

AU - Ruibal, Paula

AU - Oestereich, Lisa

AU - Lüdtke, Anja

AU - Becker-Ziaja, Beate

AU - Wozniak, David

AU - Kerber, Romy

AU - Korva, Misa

AU - Cabeza-Cabrerizo, Mar

AU - Bore, Joseph

AU - Koundouno, Fara Raymond

AU - Duraffour, Sophie

AU - Weller, Romy

AU - Thorenz, Anja

AU - Cimini, Eleonora

AU - Viola, Domenico

AU - Agrati, Chiara

AU - Reptis, Johanna

AU - Afrough, Babak

AU - Cowley, Lauren

AU - Ngabo, Didier

AU - Hinzmann, Julia

AU - Mertens, Marc

AU - Vitoriano, Ines

AU - Logue, Christopher

AU - Boettcher, Jan Peter

AU - Pallasch, Elisa

AU - Sachse, Andreas

AU - Bah, Amadou

AU - Nitzsche, Katja

AU - Kuisma, Eeva

AU - Michel, Janine

AU - Holm, Tobias

AU - Zekeng, Elsa-Gayle

AU - García-Dorival, Isabel

AU - Wölfel, Roman

AU - Stoecker, Kilian

AU - Fleischmann, Erna

AU - Strecker, Thomas

AU - Di Caro, Antonino

AU - Avšič-Županc, Tatjana

AU - Kurth, Andreas

AU - Meschi, Silvia

AU - Mély, Stephane

AU - Newman, Edmund

AU - Bocquin, Anne

AU - Kis, Zoltan

AU - Kelterbaum, Anne

AU - Molkenthin, Peter

AU - Carletti, Fabrizio

AU - Portmann, Jasmine

AU - Wolff, Svenja

AU - Castilletti, Concetta

AU - Schudt, Gordian

AU - Fizet, Alexandra

AU - Ottowell, Lisa

AU - Herker, Eva

AU - Jacobs, Thomas

AU - Kretschmer, Birte

AU - Severi, Ettore

AU - Ouedraogo, Nobila

AU - Lago, Mar

AU - Negredo, Anabel

AU - Franco, Leticia

AU - Anda, Pedro

AU - Schmiedel, Stefan

AU - Kreuels, Benno

AU - Wichmann, Dominic

AU - Addo, Marylyn

AU - Lohse, Ansgar

AU - De Clerck, Hilde

AU - Nanclares, Carolina

AU - Jonckheere, Sylvie

AU - Van Herp, Michel

AU - Sprecher, Armand

AU - Xiaojiang, Gao

AU - Carrington, Mary

AU - Miranda, Osvaldo

AU - Castro, Carlos

AU - Gabriel, Martin

AU - Drury, Patrick

AU - Formenty, Pierre

AU - Diallo, Boubacar

AU - Koivogui, Lamine

AU - Magassouba, N'Faly

AU - Carroll, Miles

AU - Günther, Stephan

AU - Muñoz-Fontela, Cesar

PY - 2016/5/5

Y1 - 2016/5/5

N2 - Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD1. In particular, very little is known about human immune responses to Ebola virus2,3. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4+ and CD8+ T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.

AB - Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD1. In particular, very little is known about human immune responses to Ebola virus2,3. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4+ and CD8+ T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.

U2 - 10.1038/nature17949

DO - 10.1038/nature17949

M3 - Letter

SN - 0028-0836

VL - 533

SP - 100

EP - 104

JO - Nature

JF - Nature

ER -

Unique human immune signature of Ebola virus disease in Guinea

Abstract

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